Nitrous oxide for the treatment of complex regional pain syndrome: a randomized blinded trial.

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a debilitating neuropathic condition often refractory to conventional treatments. N-methyl-D-aspartate (NMDA) receptor antagonists have a well-established role in the development and modulation of chronic neuropathic pain. Nitrous oxide is widely used and generally safe anesthetic gas with NMDA receptor antagonist activity. We therefore tested the hypothesis that brief periods of nitrous oxide exposure reduce pain in patients with CRPS. METHODS: Patients with a diagnosis of CRPS were randomized to either 2 hours of nitrous oxide exposure on three alternating days (Nitrous Oxide) versus a placebo air/oxygen mixture (Air-Oxygen). Our primary outcome was patient-reported pain scores at 1 week and 1 month. Secondary and exploratory outcomes were physical and mental health (PRMOIS-29 v2 survey), specific neuropathic pain symptoms (McGill short-form questionnaire), and opioid consumption. RESULTS: 44 patients participated in the study; 20 were randomized to Nitrous Oxide and 24 were assigned to Air-Oxygen. Pain scores did not differ significantly, with the estimated difference in means (Nitrous Oxide-Air-Oxygen) of -0.57 (95% CI: -1.42 to 0.28) points, p=0.19. There were also no differences detected in secondary outcomes, with the estimated difference in mean Z-scores for physical health (Nitrous Oxide-Air-Oxygen) of 0.13 (95% CI: -0.16 to 0.43), mental health 0.087 (95% CI: -0.31 to 0.48), and Patient Global Impression of Change score -0.7 (95% CI: -1.85 to 0.46). CONCLUSIONS: Compared with air/oxygen, 2 hours of nitrous oxide/oxygen exposure for three sessions did not provide meaningful therapeutic potential for patients with chronic CRPS. Our results do not support using nitrous oxide for the treatment of CRPS.

Increased Production of Abdominal Donor Site Fluid Following Microsurgical Breast Reconstruction With Superficial Inferior Epigastric Artery Versus Deep Inferior Epigastric Artery Perforator Flaps.

Introduction and aims Donor site seroma following abdominal flap harvest for breast reconstruction is common in both deep inferior epigastric artery perforator (DIEP) and superficial inferior epigastric artery (SIEA) flaps. We tested the hypothesis that there is increased donor site fluid following SIEA dissection compared to DIEP. Materials and methods Of60 SIEA breast reconstructions performed by one surgeon in 50 patients (2004-2019), complete data were available for 31 patients. Eighteen unilateral SIEAs were matched with 18 unilateral DIEPs. Thirteen bilateral flap harvests involving an SIEA were matched with 13 bilateral DIEP controls. Their cumulative abdominal drain outputs, times to drain removal, hospital stay, and number and volume of seroma aspirations were compared. Results Patients who underwent an SIEA flap harvest had significantly increased drain output compared to only a DIEP flap harvest (SIEA=1,078 mL, DIEP=500 mL, p<0.001), which remained significant after controlling for confounding variables (p=0.002). There was increased time until drain removal (SIEA=11 days, DIEP=6 days, p=0.010), and patients who underwent an SIEA harvest were 14 times more likely to be discharged with a drain in situ (odds ratio (OR)=14.6, 95% confidence interval (CI)=2.8203-75.9565, p=0.0014). There was no significant difference in the number or volume of outpatient aspirations, length of hospital admission, or total seroma volume. Conclusion This study demonstrated that SIEA harvest is a significant predictor of increased abdominal drain output postoperatively. This accounted for longer periods before drain removal and more patients discharged with an abdominal drain in situ and should be an important consideration for reconstructive surgeons. There was no demonstrable difference in the number or volume of seroma aspirations after drain removal for either group.

Association Between Mobilization and Composite Postoperative Complications Following Major Elective Surgery.

Importance: Mobilization after surgery is a key component of Enhanced Recovery after Surgery (ERAS) pathways. Objective: To evaluate the association between mobilization and a collapsed composite of postoperative complications in patients recovering from major elective surgery as well as hospital length of stay, cumulative pain scores, and 30-day readmission rates. Design, Setting, and Participants: This retrospective observational study conducted at a single quaternary US referral center included patients who had elective surgery between February 2017 and October 2020. Mobilization was assessed over the first 48 postoperative hours with wearable accelerometers, and outcomes were assessed throughout hospitalization. Patients who had elective surgery lasting at least 2 hours followed by at least 48 hours of hospitalization were included. A minimum of 12 hours of continuous accelerometer monitoring was required without missing confounding variables or key data. Among 16 203 potential participants, 8653 who met inclusion criteria were included in the final analysis. Data were analyzed from February 2017 to October 2020. Exposures: Amount of mobilization per hour for 48 postoperative hours. Outcomes: The primary outcome was a composite of myocardial injury, ileus, stroke, venous thromboembolism, pulmonary complications, and all-cause in-hospital mortality. Secondary outcomes included hospital length of stay, cumulative pain scores, and 30-day readmission. Results: Of 8653 included patients (mean [SD] age, 57.6 [16.0] years; 4535 [52.4%] female), 633 (7.3%) experienced the primary outcome. Mobilization time was a median (IQR) of 3.9 (1.7-7.8) minutes per monitored hour overall, 3.2 (0.9-7.4) in patients who experienced the primary outcome, and 4.1 (1.8-7.9) in those who did not. There was a significant association between postoperative mobilization and the composite outcome (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84; P < .001) for each 4-minute increase in mobilization. Mobilization was associated with an estimated median reduction in the duration of hospitalization by 0.12 days (95% CI, 0.09-0.15; P < .001) for each 4-minute increase in mobilization. The were no associations between mobilization and pain score or 30-day readmission. Conclusions and Relevance: In this study, mobilization measured by wearable accelerometers was associated with fewer postoperative complications and shorter hospital length of stay.

Postoperative oxygenation assessed by SpO2/FiO2 ratio and respiratory complications after reversal of neuromuscular block with Sugammadex or neostigmine: A retrospective cohort study.

STUDY OBJECTIVE: Residual neuromuscular block may lead to postoperative muscle weakness, inadequate oxygenation, and other pulmonary complications. Sugammadex may provide more rapid and effective restoration of neuromuscular function than neostigmine. We therefore tested the primary hypothesis that noncardiac surgical patients given sugammadex oxygenate better during initial recovery than those given neostigmine. Secondarily, we tested the hypothesis that patients given sugammadex have fewer pulmonary complications during hospitalization. DESIGN: Retrospective cohort analysis. SETTING: Postoperative recovery area of a tertiary care hospital. PATIENTS: Adults who had non-cardiothoracic surgery and were given either neostigmine or sugammadex. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was the lowest SpO2/FiO2 ratio in the post-anesthesia care unit. The secondary outcome was a composite of pulmonary complications. MAIN RESULTS: Among 71,457 cases, 10,708 (15%) were given sugammadex and 60,749 (85%) received neostigmine. After propensity weighting, the mean minimum SpO2/FiO2 ratio was 301 ± 77 (SD) in patients given sugammadex and 303 ± 71 in those given neostigmine, yielding an estimated difference in means of -3.5 (95% confidence interval: -5.3, -1.7; P = 0.0002). 4.4% of patients given sugammadex and 3.6% of patients given neostigmine had postoperative pulmonary complications (P = 0.0005, number-needed-to-be-exposed =136; 95% CI: 83, 330), with the main contributing components being new bronchospasm or exacerbation of obstructive pulmonary disease. CONCLUSIONS: Postoperative minimum SpO2/FiO2 ratio during PACU admission was similar after reversal of neuromuscular block by sugammadex and neostigmine. Reversal with sugammadex was associated with more pulmonary complications, but most were minor and of little consequence.

The association of hemoglobin with postoperative delirium and atrial fibrillation after cardiac surgery: a retrospective sub-study.

BACKGROUND: Most cardiac surgery patients experience postoperative anemia. Delirium and Atrial Fibrillation (AF) are common and independent predictors of morbidity and mortality. Few reports examine their association with postoperative anemia. This study aims to quantify the association between anemia and these outcomes in patients undergoing cardiac surgery. METHODS: This post-hoc analysis of the DECADE randomized controlled trial ran at six academic US hospitals. Patients aged 18-85 years with heart rate > 50 bpm undergoing cardiac surgery who had daily hemoglobin measurements in the first 5 Postoperative Days (POD) were included. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU (CAM - ICU), preceded by the Richmond Agitation and Sedation Scale, with patients excluded from assessment if sedated. Patients had daily hemoglobin measurements, continuous cardiac monitoring plus twice-daily 12-lead electrocardiograms, up to POD4. AF was diagnosed by clinicians blinded to hemoglobin levels. RESULTS: Five hundred and eighty-five patients were included. Mean postoperative hemoglobin Hazard Ratio (HR): 0.99 (95% CI 0.83, 1.19; p = 0.94) per 1 g.dL-1 hemoglobin decrease. 197 (34%) developed AF, mainly on POD = 2.3. Estimated HR = 1.04 (95% CI 0.93, 1.17; p = 0.51) per 1 g.dL-1 hemoglobin decrease. CONCLUSIONS: Most patients undergoing major cardiac surgery were anemic in the postoperative phase. AF and delirium occurred in 34% and 12% of patients, respectively, but neither were significantly correlated with postoperative hemoglobin.

Perioperative Myocardial Injury.

An increasing body of evidence suggests that a postoperative rise in cardiac troponin, even in the absence of other diagnostic criteria for myocardial infarction, is still associated with a range of postoperative complications including myocardial death and all-cause mortality. Myocardial injury after non-cardiac surgery is the term used to describe these cases. The true incidence of myocardial injury after non-cardiac surgery is unknown and likely underestimated. The strength of correlation with postoperative complications is also uncertain as are likely risk factors - though these are likely similar to those for infarction given the similar pathological mechanism. This review article seeks to summarise the literature which has been published over the preceding decades addressing these questions.

The History of Surgical Education in the United States: Past, Present, and Future.

In just over 100 years, surgical education in the United States has evolved from a disorganized practice to a refined system esteemed worldwide as one of the premier models for the training of physicians and surgeons. But in the changing environment of health care, new challenges have arisen that could warrant a reform. To design our future, we must understand our past. The present work is not intended to be a comprehensive account of the history of American surgery. Instead, it tells the abridged history of surgical education in our country: the evolution from apprenticeships to residencies; the birth of hospital-based teaching; the impact of key historical events on training; the marks left by some preeminent characters; the conception of regulatory entities that steer our education; and, finally, how our process of training surgeons might need to be refined for the continued progress of our profession. Told in chronological order in a manner that will be memorable to readers, this story weaves together the key events that explain how our current surgical training models came to be. We conclude with a timely invitation to draw from these past lessons to redesign the future of graduate medical education, making a case for the transition to time-variable, competency-based medical education for surgical residency programs in America.

Outcomes of Furlow Double-Opposing Z-Plasty Palatoplasty for the Treatment of Symptomatic Overt and Occult Submucous Cleft Palate: A Comparison Study.

BACKGROUND: The submucous cleft palate can be overt or occult and may require surgical repair. The double-opposing Z-plasty (Furlow repair) is the authors' center's preferred approach. This study evaluated complication rates, differences in outcome between overt and occult types, and patient factors associated with surgical failure. METHODS: This retrospective study reviewed documentation on all patients who underwent Furlow Z-plasty for submucous cleft palate at a single center between 2004 and 2018. Speech pathology was quantified using the Pittsburgh Weighted Speech Score. RESULTS: A total of 351 patients were included (125 overt and 226 occult cases). Furlow Z-plasty was successful (postoperative Pittsburgh Weighted Speech Score <7 without recommendation for secondary speech surgery) in 291 patients (82.1 percent). Apart from those requiring secondary surgery, there were no documented complications. Occult-type patients were 7.5 years old at palatoplasty with a speech score of 14.1; overt-type patients were 6.5 years old with a score of 15.7. Postoperative speech scores were similar for both groups. Secondary speech surgery patients had a higher preoperative score (16.9 versus 14.2). Age at time of palatoplasty and submucous cleft palate type were not predictive of the need for secondary surgery. Syndromic patients had higher preoperative and postoperative speech scores (15.6 and 7.5, respectively) than nonsyndromic patients (14.3 and 4.3) and needed secondary surgery more often (24.4 percent versus 9.2 percent). V-shaped velar vaulting on preoperative assessment was present in 92 percent of occult-type patients. CONCLUSIONS: Furlow palatoplasty is a safe and effective means of repairing submucous cleft palate. Patients with the occult type presented later with a lower Pittsburgh Weighted Speech Score. High preoperative speech score and syndromic status were associated with the need for secondary speech surgery. V-shaped velar vaulting is a reliable sign of occult submucous cleft palate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Cone-Beam Computed Tomography Incidental Findings in Individuals With Cleft Lip and Palate.

OBJECTIVES: The use of cone-beam computed tomography (CBCT) is well-established in clinical practice. This study seeks to categorize and quantify the incidental finding (IF) rate on CBCT in patients with cleft lip and palate (CLP) prior to orthodontic or surgical treatment. METHODS: This is systematic retrospective review of head and neck CBCTs in patients with nonsyndromic CLP taken between 2012 and 2019 at a single tertiary referral center. All assessments were performed independently by 4 observers (a head and neck radiologist and 3 orthodontists, including 2 fellowship-trained cleft-craniofacial orthodontists ). The images were divided into 9 anatomical areas and screened using serial axial slices and 3D reconstructions. The absolute number of IFs was reported for each area and statistical analysis was performed. RESULTS: Incidental findings were found in 106 (95.5%) of the 111 patients. The most common sites were the maxilla (87.4%, principally dental anomalies), paranasal sinuses (46.8%, principally inflammatory opacification), and inner ear cavities (18.9%, principally inflammatory opacification). Eleven patients had skull malformations. Thirty-three patients had IFs in 1 anatomical area, 49 patients in 2 anatomical areas, 19 patients in 3 areas, and 5 patients presented with IFs in 4 of the 9 anatomical areas. DISCUSSION: In patients with CLP, IFs on CBCT exam were present in the majority of cases. Most patients with IFs had them in multiple anatomical areas of the head and neck. The maxillary dental-alveolar complex was the most common area. Inflammatory changes in the inner ear cavities and paranasal sinuses were also common; however, cervical spine and skull abnormalities were also identified. Clinicians caring for patients with CLP should be aware of IFs, which may warrant further investigation and treatment.

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 µm2) compared to autograft (4.62 ± 3.99 µm2) and PCL/Empty (4.52 ± 5.16 µm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

Interleukin-10 Does Not Augment Osseous Regeneration in the Scarred Calvarial Defect Achieved with Low-Dose Biopatterned BMP2.

BACKGROUND: Large calvarial defects represent a major reconstructive challenge, as they do not heal spontaneously. Infection causes inflammation and scarring, further reducing the healing capacity of the calvaria. Bone morphogenetic protein-2 (BMP2) has been shown to stimulate osteogenesis but has significant side effects in high doses. BMP2 has not been tested in combination with antiinflammatory cytokines such as interleukin-10. METHODS: Sixteen New Zealand White rabbits underwent 15 × 15-mm flap calvarectomies. The flap was incubated in Staphylococcus aureus and replaced, and infection and scarring were allowed to develop. The flap was subsequently removed and the wound débrided. A 15 × 15-mm square of acellular dermal matrix biopatterned with low-dose BMP2, interleukin-10, or a combination was implanted. Computed tomographic scans were taken over 42 days. Rabbits were then killed and histology was performed. RESULTS: Defects treated with BMP2 showed significantly (p < 0.05) greater osseous regeneration than untreated controls. Interleukin-10 did not significantly augment the healing achieved with BMP2, and interleukin-10 alone did not significantly increase healing compared with controls. Histology showed evidence of bone formation in defects treated with BMP2. Untreated controls and defects treated with interleukin-10 alone showed only fibrous tissue in the defect site. CONCLUSIONS: Low-dose BMP2 delivered directly to the scarred calvarial defect augments bony healing. Interleukin-10 at the dose applied did not significantly augment healing alone or in combination with BMP2. Healing had not finished at 42 days and analysis at later time points or the use of higher doses of BMP2 may yield greater healing.

The Future of Facial Fat Grafting.

Fat grafting was first described in the early 20th century but for many years remained a relatively underused technique due to the unreliability of long-term volume expansion. Significant improvements in reliability have been made in the last 2 decades and there is a large body of literature pertaining to extraction, processing and injection methods to obtain more lasting effects. However, volume loss and graft resorption remain a major challenge in the long term and lead to unpredictability in results. Enriching adipose graft with stromal vascular fraction, ex vivo cultured adipose stem cells and platelet-derived growth factor among others is one method under active investigation which may assist graft survival through a range of mechanisms including increased angiogenesis. Breaking adipose graft into smaller fragments such that engrafted cells have greater access to donor-site oxygenation and nutrition is another method which in theory may promote survival. Presently, adipose grafting in the face is usually for the addition of volume to fill defects. However, the stem-cell containing fraction of adipose grafting (stromal vascular fraction) appears to exert a rejuvenating effect on overlying skin and soft tissue when administered alone. The application of these low-volume injections represents a significant shift in thinking away from mere volume expansion. These techniques have been tested in a range of animal models and some human studies. In this review, the authors provide a broad overview of present research and highlight both limitations in previous research and current areas of investigation.

Reconstruction of a Calvarial Wound Complicated by Infection: Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor.

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.

Cervical Spine Injury From Unrecognized Craniocervical Instability in Severe Pierre Robin Sequence Associated With Skeletal Dysplasia.

Pierre Robin Sequence (PRS) can be associated with skeletal dysplasias, presenting with craniocervical instability and devastating spinal injury if unrecognized. The authors present the case of an infant with PRS and a type II collagenopathy who underwent multiple airway-securing procedures requiring spinal manipulation before craniocervical instability was identified. This resulted in severe cervical cord compression due to odontoid fracture and occipitoatlantoaxial instability. This case highlights the importance of early cervical spine imaging and cautious manipulation in infants with PRS and suspected skeletal dysplasia.

Obstetrical brachial plexus palsy: Can excision of upper trunk neuroma and nerve grafting improve function in babies with adequate elbow flexion at nine months of age?

Accepted indications for exploration in obstetrical brachial plexus palsy (OBPP) vary by center. Most agree that full elbow flexion against gravity at nine months of age implies high chance of spontaneous recovery and thus excludes a baby from surgical intervention. However, there are certain movements of the shoulder and forearm that may not be used frequently by the infant, but are extremely important functionally as they grow. These movements are difficult to assess in a baby and may lead to some clinicians to recommend conservative treatment, when this cohort of infants may in fact benefit substantially from surgery. A retrospective review was conducted on all infants managed surgically at the Brachial Plexus Center of a major children's hospital from 2009 to 2014. Further analysis identified five patients who had near-normal AMS scores for elbow flexion but who had weakness of shoulder abduction, flexion, external rotation, and/or forearm supination. In contrast to standard conservative management, this cohort underwent exploration, C5-6 neuroma excision, and sural nerve grafting. Data analysis was performed on this group to look for overall improvement in function. During an average follow-up period of 29 months, all patients made substantial gains in motor function of the shoulder and forearm, without loss of elbow flexion or extension, or worsening of overall outcome. In select infants with brachial plexus injuries but near-normal AMS scores for elbow flexion, surgical intervention may be indicated to achieve the best functional outcome.

Costal bone abnormalities: an unusual cause of spontaneous bilateral breast implant deflation†.

Augmentation mammoplasty is the most common aesthetic surgical procedure performed in the USA. Prosthetic failure is a major reason for surgical reintervention. A number of causes for this have been documented, but costal bone abnormalities leading to perforation of the prosthesis are very unusual. We present the case of a woman who experienced spontaneous deflation of both saline implants in close succession, and who was found to have sharp bony spicules on both sides of her chest. Pathology examination reported reactive changes, suggestive of heterotopic bone. Examination of the implants showed no defects besides small punctures on the back wall, which coincided with the position of the spicules of bone. There are a number of possible causes for these bony growths which we examine in turn. The chest wall should be examined in all cases where unexplained implant deflation has occurred.